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V.   ANABOLIC STRATEGY
       (The Rationale for the use of Anabolic Hormones)

The successful correction of lean mass loss and prevention of a severe protein deficiency in the presence of catabolic illness requires an increase in overall anabolism.

Even in the recovery phase, endogenous anabolic activity remains depressed. This is the case in elderly patients, those with chronic illness, or patients with involuntary weight loss. Adequacy of substrate (1.5 g/kg/d protein) may not be sufficient to jump-start restoration of lean body mass. However, the machinery is capable of a very rapid rate of protein synthesis that is not age-dependent if stimulated by anabolic agents.

Body composition studies during correction of protein energy malnutrition (PEM) have demonstrated that a significant portion of weight gain after unintentional weight loss from catabolic disease represents the addition of body fat and extracellular fluid, not added protein mass. Inadequate anabolic stimulation is the cause.

The action of all anabolic agents currently in clinical use is twofold. First, amino acids are driven into the protein synthesis channel in the cell thru action of cell surface receptors in lean mass. The metabolic pathways used by anabolic agents to achieve protein synthesis may be different, but the outcome is increased lean mass. The second action is anticatabolic. All anabolic agents appear to decrease protein degradation, possibly by blocking cell cortisol receptors.

In the absence of a sufficient anabolic activity, the energy-requiring protein synthesis pathway is underused and excess energy is stored as fat.

* Anabolic hormones are being used with increasing frequency in populations with lean mass loss or existing PEM, along with optimal nutrition and the added anabolic stimulus of resistance exercise.

Activity of Anabolic Hormones

HGH is normally produced by the pituitary gland (0.8 mg/d) and is a potent endogenous anabolic hormone. It is found in highest concentrations in childhood during the growth spurt and gradually decreases with age or chronic illness. HGH binds to specific cell receptors leading to a host of metabolic effects, some due to direct hormone activity on tissues, especially in the liver. Other effects are due to the release of insulin-like growth factor-1, which has potent wound-healing effects.

The primary stimuli for HGH release are starvation and resistance exercise. Agents such as glutamine and arginine have been reported to increase HGH release. The plasma HGH level is decreased after severe injury or sepsis, thereby decreasing normal anabolic activity. Numerous studies of exogenous HGH use in patients with trauma or burns and other injuries have demonstrated its efficacy for improving anabolism and the wound healing rate. The mechanism for improved outcomes appears to be related to maintenance of lean body mass. The average dose of HGH used is 0.1 to 0.2 mg/kg of body weight, or about 10 times the normal endogenous production. A number of complications have been reported; the most common is hyperglycemia, due to anti-insulin activity. Increased insulin is often required. In addition, HGH is very expensive, and it may increase morbidity and mortality. It must be given parenterally in certain populations at critical care.

Exogenous HGH, now obtained by a genetic engineering process, is only approved by the US Food and Drug Administration (FDA) for use in children with short stature or dwarfism. However, as an orphan drug, it has been used for its anabolic activity, especially in burn patients and patients with impaired wound healing.